30 terms

Bacitracin, Vancomycin, Daptomycin, Fosfomycin, Cycloserine, Polymixin B

How do bacitracin, vancomycin, fosfomycin, cycloserine work?
Inhibition of cell wall synthesis
How does daptomycin work?
Unique: depolarizes bacterial membrane
How do polymixins work?
Disruption of bacterial cell membranes
Bacitracin spectrum
How is bacitracin administered?
Nephrotoxic if given systemically, so given parenterally

Most commonly topically; used intramuscularly in infants with staphylococcal infections (RARE)

Poor absorption following topical application. Marketed as ointment with polymixin B (Polysporin) or neomycin (Neosporin); often used for dermatological and ophthalmic infection
How does vancomycin work? How is it classified?
Inhibits bacterial wall synthesis by inhibiting synthesis of wall phospholipids; also inhibits peptidoglycan cross-linking

It is bactericidal glycoprotein
Spectrum of Vancomycin

Gram-positive bacteria
Indications for vancomycin

First line: infection by penicillin-resistant Strep pneumoniae
Use restricted to tx of severe infection by beta-lactam-resistant GP organisms (Strep and Staph)
Primary indication of parentral vancomyicn is endocarditis or sepsis due to MRSA

First line agent for tetanus due to clostridium tetani
Also indicated for treatment of GP infection in patient allergic to beta-lactam
How is vancomycin administered
Commonly in combination with an aminoglycoside (gentamicin) for treatment of enterococcal infection (Synergistic bactericidal effect) in beta-lactam allergic patient

Employed orally for antibiotic-associated colitis due to staph or C. defficile overgrowth
Resistance to vancomycin
Plasmid-mediated reduction in drug permeability or altered target site
Administration of vancomycin
Not absorbed orally
Treatment of systemic infection by slow I.V. infusion
Inflammation allows it to penetrate meninges
Only orally for treatment of antibiotic-induced enterocolitis
Metabolism and excretion of vancomycin
Metabolism is insignificant

Excreted by glomerular filtration, so dosage must be altered in renal insufficiency
Adverse effects of vancomycin
Fever, chills, and/or phlebitis at site of infection
Flushing and shock due to histamine released following rapid infusion
How does daptomycin work?
Bactericidal (concentration dependent killing) through depolarization of membrane potential; leads to cell death through inhibition of proteins, DNA, and RNA synthesis
Antibacterial spectrum of Daptomycin
Active against GP bacteria
Similar spectrum to vancomycin; also synergistic with aminoglycosides
Indications for daptomycin
Complicated skin and soft tissue infections, bacteremia, endocarditis

Very active against S. aureus, MRSA, VRSA
Strep pyogenes, Strep agalactiae, Enterococcus faecalis (VRE), Enterococcus faecium (VRE)
Administration, metabolism and excretion of daptomycin
Must be given by I.v.; metabolism is unclear, but it is inactivated by pulmonary surfactant; 80% excreted by glomerular filtration, so dose must be modified in renal insufficiency
Adverse effects of daptomycin
GI distrubances: constipation, nausea, diarrhea, vomiting

Headache, insomnia, dizziness
Injection site reactions and skin rashes
Abnormal liver function tests, jaundice, renal failure
Fosfomycin (monurol) mechanism
Inhibits bacterial cell walls; resistance by decreased permeability; synergistic with aminoglycosides, beta lactams, or fluroquinolones
Use of fosfomycin
GP and GN organisms; Only orally; uncomplicated UTI (acute cystitis) and is safer during pregnancy; major indication is single dose treatment of UTI in female due to E. coli or Enterococcus faecalis
Pharmacokinetics of fosfomycin
Excreted by kidneys, unchanged; diarrhea is common side effect;
Cycloserine mechanism
Inhibition of cell wall synthesis
Cycloserine use
Second-line tuberculostatic agent, since it is not more active than first-line but hase more adverse effects;

Active against many GP and GN organisms, although it isn't really used for this
Pharmacokinetics of cycloserine
Widely distributed in body fluids, including CSF; metabolized to an extent; both cycloserine and metabolite eliminated by kidneys; accumulation occurs in those with renal failure
Adverse effects of cycloserine
CNS toxicity including headaches, tremors, psychosis, convulsion; peripheral neuropathy
Polymixin B mechanism
Behave like cationic detergents; bind to and disrupt bacterial cell membranes; tey are bactericidal for several GN rods
Polymixin B spectrum
Effective against GN rods, including Pseudomonas

Spectrum also includes E. coli, Enterobacter aerogenes, H. influenzae, Klebsiella pneumoniae, Shigella; GPs, as well as Preteus, Serratia, Nisseria are resistant to polymixins
Indications for Polymixin B
Corneal ulcers and external otitis by Pseudomonas infections
Pharmacokinetics of polymixin B
Sulfate salt of polymixin B is water soluble and very stable in solution; however poorly distributed to tissues

Thus, mostly limited to topical applications in ointments with neomycin or bacitracin for superficial skin lacerations

Systemic use rare due to potential for nephrotoxicity and neurotoxicity; available for parentral use in UTI and bacteremia due to susceptible GN organisms when other antibiotics are contraindicated or ineffective
Adverse effects of Polymixin B
Major is potential for nephrotoxicity when given systemically; Neurotoxicity also associated with polymixins